D-erythro-d-galacto-octopyranose derivatives



3,337,527 D-ERYTHRO-D-GALACTO-OCTOPYRANOSE DERIVATIVES Brian Bannister, Kalamazoo, and Herman Hoeksema,

Cooper Township, Kalamazoo County, Mich., assignors to The Upjohn Company, Kalamazoo, Mich., a corporation of Delaware No Drawing. Filed June 15, 1964, Ser. No. 375,334 14 Claims. (Cl. 260-210) This invention relates to novel compositions of matter and is more particularly concerned with N-acyl-2-a1kyl- 3,4-O-isopropylidene-1-deoxylincosamine [6-acylamino-2- O alkyl 1,6,8-trideoxy-3,4-O-isopropylidene-D-erythro- D-galacto-octopyranose] (VIII); N-acyl-2,7-di-O-alky1-3, 4-O-isopropy1idene-l-deoxylincosamine [6-acy1amino-2,7- di O alkyl 1,6,8-isopropylidene-D-erythro-D-galactooctopyranose] (IX); novel processes for the production of United States Patent 0 3,337,527 Patented Aug. 22, 1967 these compounds and for N-acetyl-7-O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine [6-acyiamino-7-O-alkyl- 1,6,8 trideoxy-3,4-0-isopropylidene-D-erythro-D-galactooctopyranose] (VII) and the intermediates in this process and analogues, particularly 7-O-a1kyl-1-deoxylincosamine [6 amino 1,6,8-trideoxy-7-O-alkyl-D-erythro-D- galacto-octopyranose] (XIII); 2-O-alkyl-l-deoxylincosamine [6 amino 1,6,8-trideoxy-2-O-alkyl-D-erythro-D- galacto-octopyranose] (XIV); 2,7-di-O-alkyl-l-deoxylincosarnine [6 amino 1,6,8-trideoXy-2,7-di-O-alkyl-D-erythro-D-galacto-octopyranose] (XV) and the like.

This application is a continuation-in-part of application S.N. 359,448, filed Apr. 13, 1964, now US. Patent 3,- 255,174.

The process of the present invention and the intermediate and final products therein can ,be illustratively represented in the following sequence of formulae:

wherein R is selected from the group consisting of alkyl and aralkyl containing from 1 to 11 carbon atoms, inclusive, and wherein R is an alkyl group having from 1 to 12 carbon atoms, inclusive.

Representative R groups include: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, phenyl, benzyl, phenethyl, 3-phenylbutyl, 3-phenylpentyl, branched chain isomers such as isopropyl, isobutyl, isopentyl, t-butyl, neopentyl, and the like.

Representative R groups include: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, and branched isomers thereof, and the like.

The process of the present invention comprises: treating a methyl N-acyl-u-thiolincosaminide (I) with dry acetone in the presence of an acid catalyst, for example sulfuric acid, to give a mixture of methyl N-acyl-3,4-O- isopropylidene-a-thiolincosaminide (HI) and the oxazoline derivative thereof (II); hydrolyzing compound (II) in hot water to convert it to methyl N-acyl-3,4-O- isopropylidene a thiolincosaminide (-III); methylating compound (III) with an alkyl halide selected from the group consisting of alkyl chlorides, alkyl bromides and alkyl iodides in which the alkyl group has from 1 to 12 carbon atoms, inclusive, in the presence of a base and separating the three products thus obtained: methyl N-acyl 3,4 O isopropylidiene-7-O-alkyl-ot-thionlincosaminide [methyl 6-acyl-amino-6,8dideoxy-3,4 O-isopropylidene-7-O-alkyl-l-thio D erythro-a-D-galacto-octopyranoside] (IV); methyl N-acyl-3,4-O-isopropylidene- 2-O-alkyl-a-thiolincosaminide [methyl 6-acylamino-6,8-

dideoxy 3,4 -0 isopropylidene 2 O alkyl-l-thio-D- erythro-o-D-glacto-octopyranoside] (V); and methyl N-acyl 3,4 O isopropylidene-2,7-di-O-alkyl-u-thiolincosaminide [methyl 6-acylamino-6,8-didexoy-3,4-O-isopropylidene 2,7 di- 0 alkyl 1 thio D erythro-oc-D- galacto-octopyranoside] (VI); desulfurizing compounds IV, V and VI individually with nickel catalyst in a lower alkanol to obtain N-acyl-7-Q-alkyl-3,4-O-isopropylidenel-deoxylincosamine (VII); N-acyl-2-O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine (VIII), and N-acyl-2,7- di-O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine (IX).

Compounds IV, V and VI and compounds VII, VIII and IX can be treated with a dilute mineral acid, e.'g. hydrochloric, sulfuric, and the like acids, to eliminate the isopropyidene moiety and with hydrazine to remove the acyl group attached to the amino nitrogen. In this manner the new compounds methyl-7-O-alkyl-u-thiolincosaminide (X), methyl 2-0-alkyl-u-thiolincosarninide (XI), methyl 2,7O-alkyl-a-thiolincosaminide (XII); 7-O-alkyll-deoxylincosamine (XIII), 2 O alkyl 1 lincosamine (XIV), and 2,7-di-O-a1kyl-l-deoxylincos-amine (XV) are obtained. Alternatively, compounds X, XI and X11 can be desulfurized with a nickel catalyst, e.g. Raney nickel, to give the compounds of Formulae XI-II, XIV and XV.

The novel compounds of Formulae VIII and X through XV, inclusive, are useful intermediates for the production of plastic materials. For example they can be reacted with isocyanates to form urethanes and ureas, and can be used to modify polyurethane resins. Thus, these compounds can be reacted with an excess of toluene diisocyanate to form a prepolymer which can then be reacted with polyol ethers and polyol esters, commonly used to form polyurethanes; alternatively, these compounds can be mixed with polyol compounds and the mixture then reacted with toluene diisocyante. The 2-0-, 7-0-, and 2,7-di-O-alkyl-l-deoxylineosamines and the methyl 2-O-, 7-O- and 2,7-di-O-alkyl-l-thiolincosaminides can also be reacted with ethylene oxide, propylene oxide, and like alkylene oxides to form polyoxyalkylene 2-0-, 7-0-, and 2,7-di-O-alkyl-l-deoxylincosamines and methyl 2-0-, 7-0-, and 2,7-di-O-alkyl-thiolincosaminides, which can be reacted with toluene diisocyanate to form a polyurethane. The compounds VII and VIII are particularly useful for producing rigid polyurethane foams. They also condense with formaldehyde, especially when the thiocyanic acid addition salt is employed, to form polymers according to Us. Patents 2,425,320 and 2,606,155 which are useful as pickling inhibitors. The fluosilicic acid addition salts of compounds VII, VIII and X through XV are also useful as mothproofing agents in accordance with US. Patents 2,915,334 and 2,075,359.

The novel compounds 'IV, V and VI are not only new intermediates for the productions of the novel compounds VIII and IX and the known compound VII (U.S. application Ser. No. 359,448, filed Apr. 13, 1964, now US. Patent 3,255,174), but they can also be hydrogenated to the corresponding 6-alkylamino derivatives which upon reaction with thiocyanoacetic acid yields insecticides useful, for example, in sprays against flies and mosquitoes.

In carrying out the process of the present invention,

a methyl N-acyl-ix-thiolincosaminide (I), in which the acyl group has from 2 to 12 carbon atoms, is suspended in dry acetone. An acid catalyst such as sulfuric acid, p-toluenesulfonic acid, o-toluenesulfonic acid, p-ethylbenzenesulfonic acid, or the like is added to the suspension, With sulfuric acid preferred. The acetone is generally used in large excess, such as a volume of 20 to 200 times the amount of the methyl N-acyl-a-thiolincosaminide. The acid catalyst is used in a quantity between 0.25 and by weight with respect to the acetone. The reaction can be carried out between 10 and the reflux temperature of the solution, but is generally carried out at room temperature. The reaction time is between minutes and 6 hours, depending on the temperature. After the reaction is terminated, the mixture is neutralized, inorganic salts precipitated by the neutralization are removed by filtration, and the filtrate is evaporated to give a mixture containing crystalline solids. This mixture is separated with water into a water-soluble and water-insoluble fraction; the water-soluble material is the methyl N-acyl-3,4-O-isopropylidene-a-thiolincosaminide (II-I); the insoluble fraction is the oxazoline derivative thereof (11).

The water-insoluble oxazoline derivative of methyl N-acyl-3,4-O-isopropylidene-wthiolincosaminide can be converted to methyl N-acyl-3,4 0-isopropylidene-a-thiolincosaminide by heating with water. After this hydrolysis is complete, the product is obtained by evaporating the solution until crystallization occurs.

The alkylation of the methyl N-acyl-3,4-O-isopropylidene-a-thiolincosaminides is performed with an alkyl halide, preferably an alkyl chloride, bromide or iodide, in the presence of a strong base. As alkylating agents, methyl iodide, methyl bromide, ethyl iodide, ethyl bromide, and propyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl chlorides, bromides and iodides and any of the branched-chain alkyl chlorides, bromides or iodides having up to 12 carbon atoms can be used. As a base, alkoxides, such as sodium rnethoxide, potassium methoxide, potassium isopropoxide, potassium tert-butoxide, sodium tert-butoxide, soda-mide and the like can be used. The alkylation can be performed at a temperature between 0 and 50 C. using inert solvents such as benzene, toluene, dioxane, tetrahydrofuran, and the like. After the reaction is terminatedusually between /2 hour and 3 hours-the reaction mixture is filtered to remove solids, such as sodium or potassium chloride, broachieved by heating them under reflux in ethanol with loosely packed Raney nickel for a period of 2 to 24 hours. Thereafter, the catalyst is removed by filtration and the filtrate is evaporated to give a residue which can be purified by conventional means such as recrystallization from organic solvents. In this manner are obtained N acyl 7-O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine (N-acyl-7-O-alkyl-3,4-O-isopropylidene-1,5-anhydrolincosaminol) (VII);

N acyl 2 O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine (N-acyl-2-O-alkyl-3,4-O-isopropylidene-1,5-anhydrolincosaminol) (VIII); and

N acyl 2,7-di-O-alkyl-3,4-O-isopropylidene-l-deoxylincosamine (N-acyl-2,7-di-O-alkyl-3,4-O-isopropylidene- 1,5-anhydrolincosaminol (TX).

The methyl N-acyl-3,4-isopropylidene-7-O-, -2-O-, or -2,7-di-O-alkyl-a-thiolincosaminides are converted to methyl N-acyl 7-O-, 2-0-, or 2,7-di-O-alkyl-a-thiolincosaminide by hydrolysis with a dilute mineral acid, e.g. aqueous 0.1 to 0.5 N hydrochloric, hydrobromic, sulfuric. acid or the like, with hydrochloric acid preferred. The reaction can be carried out between 10 and 50 (1., preferably at room temperature, between about 20 and 30 C. At the termination of the reaction the product is isolated by conventional methods, e..g. neutralizing the solution with an anion exchange resin such as Amberlite IRA-400, filtering to remove the resin and evaporating the solution.

The thus-obtained methyl N-acyl-2-O-, 7-0- or 2,7-di- O-aIkyl-a-thiolincosaminides are heated under reflux with hydrazine hydrate for a period of 4-48 hours, usually between 18 and 24 hours to give the corresponding methyl 7-O-alkyl-oi-thiolincosaminide (X), methyl 2-O-alkyl-uthiolincosaminide (XI), and methyl 2,7-di-O-alkyl-oi thiolincosaminide (XII). Compounds X, XI or XII in crude form are isolated from the reaction mixture by distilling excess hydrazine hydrate in vacuo. Purification of the crude material is carried out by conventional means, such as recrystallization from solvents, e.g. methanol, ethanol, ethyl acetate, Skellysolve B hexanes, mixtures thereof, and the like.

In the same maner, hydrolyzing and hydrazinolyzing N-acyl-7-O, 2-0-, or 2,7-di-O-3,4-isopropylidene-l-deoxylin-cosamine as discussed above yield 7-O-alkyl-1-deoxylincosamine (XIII), 2-O-alkyl-l-deoxylincosamine (XIV) and 2,7-di-O-alkyl-l-deoxylincosamine (XV).

The following examples are illustrative of the process and products of the present invention, but are not to be construed as limiting.

EXAMPLE 1 Methyl N-acetyl-3,4-O-is0pr0pylidene-a-thiolincosaminide (III) and the oxazoline (11) derived therefrom A. METHYL zt-IHIOLING-OSAMINIDE A solution of 4 g. of lincomycin (U.S. Patent 3,086,912) in 20 ml. of hydrazine hydrate (98100%) was refluxed for 21 hours; excess hydrazine hydrate was then removed in vacuo under nitrogen at steam bath temperature. The residue, a pasty mass of crystals, was cooled, acetonitrile was added, and the mixture was stirred until the crystals were suspended. The crystals were collected on a filter and washed with acetonitrile and with ether. The yield of white, crystalline methyl 04-.

7 thiolincosarninide after drying in vacuo at room temperature was 2.1 g. (-84%). Recrystallization was accomplished by dissolving the methyl a-thiolincosaminide in hot dimethylformamide and adding an equal volume of ethylene glycol dimethyl ether.

Methyl a-thiolincosaminide has a melting point of 225-228 C., an optical rotation of [a] |276 (c., 0.768, water), and a pKa' of 7.45.

Analysis.Calcd. for C H NO S: C, 42.7; H, 7.56; N, 5.53; S, 12.66. Found: C, 42.6; H, 7.49; N, 5.75; S, 12.38.

B. METHYL N-ACETYL-a-THI OLINCOSAMI'NIDE Five grams of methyl a-thiolincosaminide (about 0.02 mole) was suspended with stirring in 50 ml. of methanol and treated with 4.04 g. (about 0.04 mole) of acetic anhydride. The starting material dissolved almost completely, and thereafter the mixture became solid. After 18 hours at room teperat-ure (about 25 C.), the solid was filtered, washed with methanol, and dried in a vacuum oven at 50 C. and 15 mm. pressure; yield, 4.58 g. (79%) of crystalline product melting at 242-245 C. This product was recrystallized from absolute menthanol to give colorless needles of methyl N-acetyl-a-thiolincosaminide having a melting point of 243245 C. and a rotation [oc] -|265 (c., 0.7374, water).

Analysis.-Calcd. for C H NO S: C, 44.72; H, 7.17; N, 4.74; S, 10.85. Found: C, 44.87; H, 7.10; N, 4.65; S, 10.99.

c. METHYL -N-AcETYL-3,4--IsOPROPYLIDENE- a THI- OLINCOSAMINIDE AND THE OXAZOLINE DERIVED 'THEREFROM Sixteen grams of methyl N-acetyl-a-thiolincosaminide was finely powdered and suspended in 1600 ml. of dry acetone with rapid magnetic stirring. To this suspension was added 16 ml. of concentrated sulfuric acid. The suspended solid began to dissolve and solution was complete within 30 to 60 minutes. After standing for 3 hours at room temperature (2426 C.), the solution was cooled overnight in a refrigerator at about 5 to C.

The pale yellow solution was neutralized by introducing, with stirring, a steam of dry ammonia gas. Ammonium sulfate precipitated and was removed by filtration and washed with acetone. The acetone washing was added to the colorless filtrate which was evaporated on a rotating evaporator at 30 C. and mm. Hg pressure, to yield a mixture of syrup and crystalline solids. The syrup was dissolved by swirling the mixture with 50 ml. of water, and the crystalline solid was collected on a filter and washed with ice-cold water. Upon drying at 60 C. and 15 mm. Hg pressure, 7.12 g. of solids were obtained of melting point 189192 C. Recrystallization from acetone-Skellysolve B hexanes gave colorless needles of the oxazoline derived from methyl N-acetyl-3,4-O-isopropylidene-a-thiolincosaminide; melting point, 19l192.5 C.; rotation [cc] +l26 (0., 0.8508, ethanol).

Analysis.-Calcd. for C H NO S: C, 52.95; H, 7.30; N, 4.41; S, 10.10; 0, 25.20. Found: C, 52.77; H, 7.34; N, 4.40; S, 10.12; 0, 25.11.

The aqueous mother liquors were concentrated in vacuo to give a solid which was recrystallized from acetone; it consisted of methyl N-acetyl-3,4-0-isopropylidene-a-thiolincosaminide of melting point l78180 C. and rotation [cc] +189 (c., 0.5137, water).

EXAMPLE 2 Conversion of the oxazoline derived from methyl N-acetyl 3,4-O-isopr0pylidene a-thiolincosaminide to methyl N- acetyl-3,4-O-is0pr0pylidene-a-thiolincosaminide A solution was prepared of the oxazoline derived from methyl N-acetyl-3,4-O-isopropylidene-a-thiolincosaminide in ml. of hot water and heated under reflux for 2 hours at which time thin-layer chromatography on silica gel revealed the conversion of the starting material to methyl N -acetyl-3,4-0-isopropylidene-a-thiolincosaminide.

The water was then removed in vacuo at 40 C., leaving a colorless crystalline solid which was recrystallized from a small volume of hot water to give colorless needles of methyl N-acetyl-3,4-O-isopropylidene-a-thiolincosaminide of melting point 178l80 C. and rotation [a] +190 (c., 1.223, water).

EXAMPLE 3 Methyl N-propionyl-3,4-O-isopr0pylidene a-thiolincosaminide and the oxazoline derived therefrom In the manner given in Example 1B, methyl a-thiolincosaminide was treated with propionic anhydride in methanol solution to give methyl N-propionyl-oi-thiolincosaminide.

The thus-obtained methyl N-propionyl-a-thiolincosaminide was finely powdered and suspended in dry acetone. Thereto was added water-free ethylbenzenesulfonic acid and the mixture heated to 40 C. with rapid stirring for a period of 45 minutes. It was then allowed to stand at room temperature for 5 hours before neutralization with ammonia gas as in Example l-C. The precipitated ammonium ethylbenzenesulfonate was removed by filtration and the filtrate was evaporated to dryness. The residue was treated with water and the crystalline material which did not dissolve was collected by filtration and recrystallized from acetone-Skellysolve B to give in crystalline form the oxazoline derived from methyl N-propionyl- 3,4-O-isopropylidene-u-thiolincosaminide. The mother liquors were evaporated in vacuo to give methyl N-propionyl-3,4-O-isopropylidene-u-thiolincosaminide.

In the manner given in Example 2, the oxazoline derived from methyl N-propionyl-3,4-O-isopropylidene-athiolincosaminide can be converted to methyl N-propionyl-3,4-O-isopropylidene-a-thiolincosaminide by heating the product with water.

By treating methyl a-thiolincosaminide in the manner given in Example 1-B with other anhydrides for example butyric anhydride, valeric anhydride, hexanoic anhydride, benzoic anhydride, heptanoic anhydride, phenylacetic anhydride, octanoic anhydride, phenylpropionic anhydride, nonanoic anhydride, decanoic anhydride, undecanoic anhydride, lauric anhydride and the like, other methyl N- acyl-wthiolincosaminides, such as methyl N-butyryl-, N- valeryl-, N-hexanoyl-, N-benzoyl-, 'N-phenylacetyb, N- heptanoyl-, N-octanoyl-, N-phenylpropionyl-, N-nonanoyl-, N-decanoyl-, N-undecanoyland N-lauroyl-a-thiolincosaminide.

In the manner given in Example 1-C, these methyl N-acyl-a-thiolincosaminides can be converted to the corresponding methyl N-acyl-3,4-O-isopropylidene a thiolincosaminides and the oxazolines derived therefrom, each pair of which can be separated into its components by their distinctive water-solubilities. Representative compounds thus obtained include methyl N-butyryl-, N-valeryl-, N-hexanoyl-, N-heptanoyl-, N-benzoyl-, N-phenylacetyl-, N-phenylpropionyl-, N-octanoyl-, N-nonanoyl-, N-decanoyl-, N-undecanoyland N-lauroyl-3,4-O-isopropylidene-a-thiolincosaminide and the oxazolines derived therefrom.

In the manner given in Example 2, the above oxazolines can be converted to the corresponding methyl N-acyl- 3,4-O-isopropylider1e-m-thiolincosaminide, already mentioned above.

EXAMPLE 4 Methylation of methyl N-acetyl-3,4-O-is0pr0pylidene-athiolincosaminide Potassium metal (1.16 g.) was dissolved in ml. of t-butyl alcohol (previously dried over sodium metal) under stirring and reflux. The solvent was removed as completely as possible by distillation and finally by distillation in a vacuum of 15 mm. Hg. To the dry, solid residue was added 100 ml. of dry benzene, which was removed by distillation to leave a fine powder. This was treated again with benzene which was distilled oil to insure complete removal of tert-butyl alcohol.

To the thus-obtained, powdery potassium tert-butoxide was added 200 ml. of dry benzene and the mixture was stirred magnetically at room temperature until an opalescent suspension resulted. To this was added 5 g. of methyl N-acetyl-3,4--isopropylidene-u-thiolincosaminide and the mixture was then stirred overnight at room temperature at the end of which time all of the solid had dissolved.

To this mixture was added 42.4 g. (18.6 ml.) of methyl iodide and the mixture was stirred at room temperature for 1 hours; after 1 hour, the mixture gave a neutral reaction with moist pH paper. The reaction mixture was filtered to remove potassium iodide and the potassium iodide was washed with benzene; the benzene was added to the filtrate. The filtrate and washings were distilled in vacuo at 35 Cato give a colorless syrup which was subjected to counter current distribution in the system ethyl acetatezethanohwater in the ratio 4:1:2. After 500 transfers the three components, as indicated by thin-layer chromatography, had been completely resolved. The major components were shown to be methyl N-acetyl- 3,4-Oisopropylidene-7-O-methy1 a thiolincosaminide (IV, R =R =CH and methyl N-acetyl-3,4-O-isopropylidene 2 0 methyl 0c thiolincosaminide (V, R =R =CH In addition a minor component was found, which was methyl N-acetyl-3,4-O-isopropylidene- 2,7di-O-rnethyl-a-thiolincosaminide (VI, R =R =CH Removal of solvents from combined tubes No. 250 310 (K=1.30) inclusive gave a glassy material which crystallized from ethyl acetate:Skellysolve B hexanes to yield methyl N-acetyl-3,4-O-isopropylidene-Z-O-methyI-uthiolincosaminide as short, colorless prisms of melting point 176-177 C. and rotation [u] +176 (0., 0.6220, chloroform).

Analysis. Calcd. for C H NO S: C, 51.57; H, 7.79; N, 4.01; S, 9.17; OMe, 8.88. Found: C, 51.82; H, 8.10; N, 4.08; S, 8.94; OMe, 8.49.

Removal of solvents from combined tubes No. 330-384 (K=2.52) inclusive by distillation gave a glassy product which crystallized slowly on standing. Recrystallization fromether gave clusters of minute, colorless needles of methyl N acetyl-7-O-methyl-3,4-O-isopropylidene-a-thiolincosaminide (IV, R =RFCH3L Similarly, evaporation of the solvents from combined tubes No. 410-450 (K=5.67) gave a colorless glassy product. Recrystallization from ether gave colorless, chunky needles of methyl N-acetyI-ZJ-di-O methyl-B,4-0- isopropylidene a thiolincosaminide (VI, R =R =CH of melting point 124.5126 C. and rotation [a] +184 (c., 08390, chloroform).

Analysis.-Calcd. for C H NO S: C, 52.88; H, 8.04; N, 3.85; S, 8.82; OCH 17.08. Found: C, 53.02; H, 7.95; N, 4.05; S, 8.73; OCH 15.92.

EXAMPLE Ethylation of methyl N-acetyl-3,4-0-is0pr0pylidene-athiolincosaminide In the manner given in Example 4, a solution of methyl N-acetyl-3,4-O-isopropy1idene-m-thiolineosaminide in benzene containing potassium tert-butoxide was treated with ethyl iodide to give methyl N-acetyl-3,4-O-isopropylidene- 7-O-ethyl-a-thiolincosaminide, methyl N-acetyl-3,4-O-isoprbpylidene-Z-O-ethyl-u-thiolincosaminide, and methyl N- acetyl-3,4-0-isopropylidene-2,7-di-O-ethyl a thiolincosaminide, which can be separated by counter current distribution as shown in Example 4.

EXAMPLE 6 Methylation of methyl N-propionyl-3,4-0-isapropylidenea-thiolincosaminide In the manner given in Example 4, methyl N-propionyl 3,4-O-isopropylidene-a-thiolincosaminide in benzene solution was reacted with methyl iodide in the presence of potassium t-butoxide to give methyl N-propionyl-3,4-0-isopropylidene-7-O-methyl a thiolincosaminide, methyl N-propionyl-B,4-O-isopropylidene-2-O- methyl-a-thiolincosaminide, and methyl N-propionyl-3,4- O-isopropylidene-2,7-di-O-methyl-ot-thiolincosaminide.

EXAMPLE 7 Butylation of methyl N-benzoyl-3,4-0-is0pr0pylidene-otthiolincosaminide In the manner given in Example 4, methyl N-benzoyl- 3,4-O-isopropylidene-a-thiolincosaminide, dissolved in benzene, is reacted with butyl iodide in the presence of potassium t-butoxide to give methyl N-benzoyl-3,4-O- isopropylidene-7-O-butyl-ot-thio1incosaminide, methyl N- benzoyl 3,4 O isopropylidene-2-O-butyl-u-thiolincosaminide and methyl N-benzoyl-3,4-O-isopropylidene-2,7- di-O-butyl-tat-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE 8 H exylation of methyl N-hexanoyl-3,4-0-is0pr0pylidene-uthiolincosaminide In the manner given in Example 4, methyl N-hexanoyl- 3,4-O-isopropylidene-a-thiolincosaminide, dissolved in benzene, is reacted with hexyl iodide in the presence of potassium t-butoxide to give methyl N-hexanoyl-BA- O isopropylidene-7-O-hexyl-a-thiolincosaminide methyl N-hexanoyl-3,4-0-isopropylidene-2-O hexyl 0c thiolincosaminide and methyl N-hexanoy1-3,4-O-isopnopylidene-2,7-di-O-hexyl-tit-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE 9 Octylation of methyl N-valeryl-3,4-0-is0pr0pylidene-athiolincosaminide EXAMPLE l0 Decylatz'on of methyl N-acetyl-3,4-O-isopropylidene-athiolincosaminide In the manner given in Example 4, methyl N-acetyl- 3,4-O-isopropylidene a thiolincosaminide, dissolved in benzene, is reacted with decyl iodide in the presence of potassium tert-butoxide to give methyl N-acetyl-3,4-O- isopropylidene-7-O-decyl-u-thiolincosarninide, methyl N- acetyl-3,4-O-isopropylidene 2 O decyl-a-thiolincosaminide and methyl N-acetyl-3,4-O-isopropylidene-2,7-di- O-decyl-tat-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE l1 Undecylatzon of methyl N-pr0pi0nyl-3,4-O-isopropylidene-ut-thiolincosaminide' In the manner given in Example 4, methyl N-propionyl- 3,4-O-isopropylidene 0L thiolincosaminide, dissolved in benzene, is reacted with undecyl iodide in the presence of potassium tert-butoxide to give methyl N-propionyl-3,4- O isopropylidene 7 O-undecyl-oa-thiolincosaminide, methyl N propionyl-3,4O-isopropylidene-Z-O-undecylu-thiolincosaminide and methyl N-propionyl-3,4-O-isopropylidene-2,7-di-O undecyl-u-thiolincosaminide, which are separable by counter current distribution.

I 1 EXAMPLE 12 Dodecylation of methyl N-butyryl-3,4-O-isopropylideneot-thiolincosaminide In the manner given in Example 4, methyl N-butyryl- 3,4- isopropylidene-u-thiolincosaminide, dissolved in benzene, is reacted with dodecyl iodide in the presence of potassium tert-butoxide to give methyl N-butyryl-3,4-O- isopropylidene 7-O-dodecyl-a-thiolincosaminide, methyl N-butyryl-3,4-O-isopropylidene-2-O dodecyl 0c thiolincosaminide and methyl N-butyryl-3,4-O-isopropylidene-2, 7-di-O-dodecyl-a-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE 13 Methylatz'on of methyl N Jauroyl-3,4-0-is0pr0pylidenea-thiolincosaminide In the manner given in Example 4, methyl N-lauroyl- 3,4-0 isopropylidenewt-thiolincosaminide, dissolved in benzene, is reacted with methyl iodide in the presence of potassium tert-butoxide to give methyl N-lauroyl-3,4-O

isopropylidene-7-O-methyl-a-thiolincosaminide, methyl N- lauroyl 3,4-0-isopropylidene-2-O-methyl-o -thiolincosaminide and methyl N-lauroyl-3,4-O-isopropylidene-2,7- di-O-methyl-ot-tl1iolincosaminide, which are separable by counter current distribution.

EXAMPLE 14 Ethylation of methyl N-lmdecan0yl-3,4-O-is0propylidene- DL-flZlOlil'lCOSLll'llillide In the manner given in Example 4, methyl N-undecanoyl-3,4-0-isopropylidene-ot-thiolincosaminide, dissolved in benzene, is reacted with ethyl iodide in the presence of potassium tert-butoxide to give methyl N-undecanoyl- 3,4-O-isopropylidene-7-O-ethyl-a-thiolincosaminide, methyl N-undecanoyl 3,4 O isopropylidene-2-O-ethy1-uthiolincosaminide and methyl N-undecanoyl-3,4-O-is0propylidene-2,7-di-O-ethyl-oc-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE 15 Pentylation of methyl N-phenylpr0pi0nyl-3,4-O-

isopropylidene-a-thiolincosaminide In the manner given in Example 4, methyl N-phenylpropionyl-3,4-O-isopropylidene-u thiolincosaminide, dissolved in benzene, is reacted with pentyl iodide in the presence of potassium tert-butoxide to give methyl N- phenylpropionyl-3,4-O-isopropylidene 7-O-pentyl-a-thiolincosaminide, methyl N-phenylpropionyl-3,4-O-isopropylidene-Z-O-pentyl-a-thiolincosaminide and methyl N- phenylpropionyl-3,4-0-isopropylidene-2,7-di O pentyla-thiolincosaminide, which are separable by counter current distribution.

EXAMPLE 16 Nonylation of methyl N-phenylacetyl-3,4-0-

isopropylidene-ot-thiolincosaminide packed Raney nickel in ethanol. This mixture was heated under reflux for 10 hours. Thereafter the mixture was filtered, the catalyst was washed with 1 liter of boiling ethanol, and the washings were combined with the filtrate. The filtrate and washings were then evaporated to dryness. The resulting product was distributed (500 transfers) in the system l-butanolzwater. The peak fractions were combined and crystallized from ethanol to give 7-O- methyl N acetyl-3,4-O-isopropylidene-l-deoxylincosamine of melting point 198-205 C. and rotation [M +7l (c., 1, 50% aqueous ethanol).

EXAMPLE 18 N -acetyl-2-0-methyl-3,4-O-isopropylidene-l deoxylincosamine (VIII) In the manner given in Example 17, methyl N-acetyl- 2-O-methyl-3,4-O-isopropylidene-a-thiolincosaminide was desulfurized with Raney nickel in ethanol at reflux temperature to give 2-O-methyl-N-acetyl-3,4-O-isopropylidene-l-deoxylincosamine.

EXAMPLE 19 N -acety l-Z ,7-di-O-methyl-3 ,4 -O-is0pr0 pylidene-I deoxylincosamine (IX) In the manner given in Example 17, methyl N-acetyl- 2,7-di-O-methyl-3,4-O-isopropylidene a thiolincosaminide was desulfurized with Raney nickel catalyst in ethanol solution at reflux to give N-acetyl-2,7-di-O-rnethyl- 3,4-O-isopropylidene-l-deoxylincosamine of melting point -153 C. and rotation [ah- +67 (c., 0.8266, 50% aqueous ethanol).

EXAMPLE 20 N -prop-ionyl-2-O-methyl-3,4-O-isopropylidene-I deoxylincosamiine In the manner given in Example 17, methyl N-propionyl-2-O-methyl-3,4-O-isopropylidene oz. thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-propionyl-2-O-methyl-3,4-0- isopropylidenel-deoxylincosamine.

EXAMPLE 21 N -pr0pi0ny l-7-0-methy l -3,4 -O-is0pr0py lidene-I deoxylincosamirte In the manner given in Example 17, methyl N-propionyl-7-O-methyl-3,4-O-isopropylidene oz thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-propionyl-7-O-methyl-3,4- O-isopropylidene-l-deoxylincosamine.

EXAMPLE 22 N-propionyl-2,7-di-O-methyl-3,4-O-is0pr0pylidene- 1 -deoxylincosa1mine In the manner given in Example 17, methyl N-propionyl-2,7-di-O-methyl-3,4-O-is0propylidene a thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-propionyl-2,7-di-O-methyl-3,4-O-isopropylidene-l-deoxylincosamine.

EXAMPLE 23 N -butyryl-2-0-d0decyl-3,4 -'0-is0pr0pylidene-1 deoxylincosamin'e In the manner given in Example 17, methyl N-butyryl- 2-O-dodecyl-3,4-O-isopropylidene-u thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-butyryl-2-O-dodecyl-3,4-O-isopropylidene-l-deoxylincosamine.

EXAMPLE 24 N -benz0y l-2-O-butyl-3 ,4 -O-isopr0py lid ene-I deoxylincosamine In the manner given in Example 17, methyl N-benzoyl- 2-O-butyl 3,4 O isopropylidene-a-thiolincosaminide 13 is desulfurized with Raney nickel in ethanol at reflux temperature to give N-bonzoyl-2-O-butyl-3,4-O-isopropylidene-l-deoxylincosamine. t

EXAMPLE 25 N -prpi0ny l-2-0-undecyl-3,4 -O-is0pr0pylidene-1 deoxylincosam in-e EXAMPLE 26 N-lauroyl-2-O-methyl-3,4-0isopropylidene-1- deoxylincosamine In the manner given in Example 17, methyl N-lauroyl- 2-O-methyl-3,4-O-isopropylidene-a thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-lauroyl-2-O-methyl-3,4 O-isopropylidene-l-deoxylincosamine.

EXAMPLE 27 N -wndeca n0yl-2-O-ethyl-3,4-O-isopropylidene-l deoxylincosamine In the manner given in Example 17, methyl N-undecanoyl-2-O-ethyl-3,4-O-isopropyliclene a thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-undecan0yl-2-O-ethy1-3,4-O- isopr-opylidene-l-deoxylincosamine.

EXAMPLE 28 N -phenylpr0pi0ny l-2,7 -di- 0 -pentyl-3,4 -0-isopropy lidene- 1 -de0xylinc0samine In the manner given in Example 17, methyl N-phenylpropiony1-2,7-di-O-pentyl 3,4-O-isopropylidene-a thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperatureto give N-phenylpropionyl-2,7-di-O- pentyl-3,4-O-isopropylidene-l-deoxylincosamine.

EXAMPLE 29 N -phenylwcetyl-2,7-di-O-n0nyl-3,4-O-is0pr0py Iidene-I deoxylincosamine In the manner given in Example 17, methyl N-phenylacetyl-2,7-di-O-nonyl-3,4-O-isopropylidene-m thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-phenylacetyl-Z,7-di-O-nonyl- 3,4-O-isopropy1idene-l-deoxylincosamine.

EXAMPLE 30 N-i z zleryl-7-0-0ctyl-3A-O isopropylidene-L deoxylincotsamine In the manner given in Example 17, methyl N-valeryl- 7-0-0ctyl-3,4-O-isopropylidene-o -thiolincosaminide is desulfurized with Raney nickel in ethanol at reflux temperature to give N-valeryl-7-O-octyl-3,4-O isopropylidene ldeoxylineosamine. Other compounds prepared in the manner given in Example 17 include:

N-heptanoyl-2-O-pentyl-3 ,4-O-isopropylidene- 1- 14 N-propionyl-2-O-decyl-3,4-O-isopropylidene-1- deoxylincosamine, N-propionyl-2,7-di-O-butyl-3,4-O-isopropylidene-1- =deoxylincosamine, N-phenylacetyl-2,7-di-O-hexyl-3,4-O-isopropylidene-1- deoxylincosamine, N-valeryl-Z,7-di-O-octyl-3,4-O-isopropy1idene-ldeoxylincosamine, N-propionyl-Z,7-di-O-dodecyl-3,4O-isopropylidene-1- deoxylincosamine, N-isovaleryl-2,7-di-O-decyl-3,4-O-isopropylidene-1- deoxylincosamine, N-propionyl-2,7-di-O-undecyl-3,4Oisopropylidene-1- deoxylincosamine, and the like.

EXAMPLE 31 Methyl 2-O-methyl-a-tltiolincrosaminide A solution of 2 g. of methyl N-acetyl-2-O-methyl-3,4- O-isopropylidene-oc-thiolincosaminide in 50 ml. of 0.25 N hydrochloric acid was magnetically stirred at room temperature (about 25 C.). The solid starting material dissolved Within minutes. After 1% hours, thin-layer chromatography showed the complete absence of starting material.

The strongly acidic solution was stirred With an anion exchange resin, Amberlite IRA-400 (OH* form) until the colorless supernatant solution gave a neutral reaction with pH paper. Filtration, Washing of the resin With water, and removal of the water from the combined filtrate and washes in vacuo gave 1.68 g. (95%) of a colorless crystalline residue which was crystallized from methanol-ether to give long colorless felted needless of methyl N-acetyl-Z- O-methyl 0c thiolincosaminide of melting point 237 238 C.

Analysis-Calcd. for C H NO S: C, 46.56; H, 7.49; N, 4.53; S, 10.36. Found: C, 46.72; H, 7.44; N, 4.37; S, 10.34.

The thus-obtained methyl N-acetyl-2-O methyl uthiolincosaminide was heated with 6 ml. of hydrazine hydrate under reflux for a period of 22 hours. The excess hydrazine hydrate was removed by distillation in vacuo and the residue was three times recrystallized from ethanol-water to give methyI-Z-O-methyI-a thiolincosaminide.

EXAMPLE 32 Methyl 7-O-methyl-ot-thiolincasaminide In the manner given in Example 31, methyl N-acetyl-7- O-methyl-3,4-O-isopropylidene-a thiolincosaminide was hydrolyzed and then hydrazinolyzed to give methyl 7-0- methyl-u-thiolincosaminide.

EXAMPLE 33 Methyl 2,7-di-O-methylm-thi0lihcosaminide In the manner given in Example 31, methyl N-acetyl- 2,7 -di-O-methyl-3 ,4-O-isopropylidene-a-thiolincosaminide was hydrolyzed and then hydrazinolyzed to give methyl 2,7-O-methyl-a-thiolincosaminide.

EXAMPLE 34 Methyl 7-O-ethyl-a-thiolin cosaminide In the manner given in Example 31, methyl N-acetyl- 7-O-ethyl-3,4-O-isopropylidenea thiolincosaminide was 1 hydrolyzed and then hydrazinolyzed to give methyl 7-0- ethyl-x-thi0lincosaminide.

EXAMPLE 35 Methyl 2-O-butyl-a-thiolinc0saminide In the manner given in Example 31, methyl N-acetyl-2- O-bntyl-3,4-O-isopropylidene-u-thiolincosaminide was hydrolyzed and then hydrazinolyzed to give methyl 2-O- butyl-wthiolincosaminide.

1 5 EXAMPLE 36 Methyl 2,7-di-O-hexyl-a-thiolincosaminide In the manner given in Example 31, methyl N-acetyl-Z, 7-di-O-hexyl-3,4-O-isopropylidene 0c thiolincosaminide was hydrolyzed and then hydrazinolyzed to give methyl 2,7-di-O-hexyl-u-thiolincosaminide.

EXAMPLE 37 Methyl Z-O-dOdeCyZ-Dt-thiolincosaminide In the manner given in Example 31, methyl N-acetyl2 O-dodecyl-3,4-O-isopropylidene-a thiolincosaminide was hydrolyzed and then hydrazinolyzed to give methyl 2-O- dodecyl-a-thiolincosaminide.

EXAMPLE 3 8 7 -O-methyl-1 -de0xylinc0samine In the manner given in Example 31, N-acetyl-7-O- methyl-3,4-O-is0propylidene 1 deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 7-O- methyl-l-deoxylincosamine.

EXAMPLE 3 9 Z-O-methyl-J-deoxylinc0samine In the manner given in Example 31, N-acetyl-Z-O- methyl-3,4-O-isopropylidene-l-deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 2-O- methyl-l-deoxylincosamine.

EXAMPLE 40 2,7-di-0-miethyl-1-de0xylinc0samine In the manner given in Example 31, N-acetyl-2,7-di-O- methyl-3,4-O-isopropylidene-1 deoxylincosarnine was hydrolyzed and subsequently hydrazinolyzed to give 2,7-di- O-methyl-l-deoxylincosamine.

EXAMPLE 41 7-O-ethyl-1-de0xylinc0samine In the manner given in Example 31, N-acetyl-7-O-ethyl- 3,4-O-isopropylidene-l-deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 7-O-ethyl-1-deoxylincosamine.

EXAMPLE 42 7-O-h exy l-1 -de0xylinc0samine In the manner given in Example 31, N-acetyl-7-O-hexyl- 3,4-O-isopropylidene-1-deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 7-O-hexyl-1-deoxylincosamine.

EXAMPLE 43 7 -O-decy l-1 -de0xylinc0samine In the manner given in Example 31, N-acetyl-7-O-decyl-3,4-O-isopropylidene-l-deoxylincosamine was hydr0- lyzed and subsequently hydrazinolyzed to give 7-O-decyll-deoxylincosamine.

EXAMPLE 44 Z-O-a'odecy l-1 -de0xy lincosamine In the manner given in Example 31, N-acetyl-Z-O- dodecyl-3,4-O-isopropylidene-l-deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 2-O- dodecyl-l-deoxylincosamine.

Example 45 2,7-O-0ctyl-1 -deoxylinc0samine In the manner given in Example 31, N-acetyl-2,7-O- octyl-3,4-O-isopropylidene-l-deoxylincosamine was hydrolyzed and subsequently hydrazinolyzed to give 2,7-di-O- octyl-l-deoxylincosarnine.

EXAMPLE 46 Z-O-ethyl-l-de0xylinc0samine from methyl 2-O- ethylot-thi0linc0saminide Two grams of methyl Z-O-ethyl-a-thiolincosaminide were dissolved in ml. of ethanol and thereto was added 25 m1. of loosely-packed Raney nickel in ethanol. This mixture was heated under reflux for 10 hours, cooled and filtered. The catalyst was washed with ml. of boiling ethanol, and the washings and filtrate were combined and evaporated to dryness. The resulting residue was distributed in the system l-butanolzwater. The peak fractions containing Z-O-ethyl-l-deoxylincosamine as determined by thin-layer chromatography were combined, evaporated and crystallized from ethanol to give 2-O-ethyl-1-deoxylincosamine.

In the manner given in Example 46, other 2-O-alkyl- 7-O-alkyland 2,7-di-O-alkyl-l-deoxylincosamines can be obtained from the corresponding methyl 2-O-alkyl-, 7-0- alkyland 2,7-di-O-alkyl-u-thiolincosaminides by desulfurization with Raney nickel.

We claim:

1. An oxazoline having the structural formula wherein R is selected from the group consisting of alkyl and aralkyl containing from 1 to 11 carbon atoms, inelusive.

2. The oxazoline derived from methyl N-acetyl-3,4-O- isopropylidene-u-thiolincosaminide.

3. A methyl O-alkyl-substituted-a-thiolincosaminide selected from the group consisting of compounds having the structural formulae:

wherein R is an alkyl group having from 1 to 12 carbon atoms, inclusive.

4. Methyl 2-O-methyl-a-thiolincosaminide. 5. Methyl 7-0-methyl-a-thiolincosaminide. 6! Methyl 2,7-di-O-methyl-a-thiolincosaminide.

7. An O-alkyl-substitute -Zdeoxylincosamine selected propylidene-2,7-di-O-alkyliiiolincosaminide from each from the group consisting of compounds having the strucother; and desulfurizing separately each of these comtural formulae: pounds with a nickel catalyst in a lower alkanol to obtain no H O OH OH H wherein R is an alkyl group having from 1 to 12 carbon 15 separately the corresponding N-acyl-2-O-a1kyl-3,4-is0- atoms, inclusive. propylidene-l-deoxylincosamine, N-acyl-7-O-alkyl-3,4-O- 8. Z-O-methyl-l-deoxylincosamine. isopropylidene-l-deoxylincosamine and N-a1ky1-2,7-di-O- 9. 7-O-methyll-deoxylincosamine. alkyl-3,4-O-isopropylidene-1-deoxylincosamine. 10. 2,7-di-O-methyl-l-deoxylincosamine. 12. The process of claim 11, wherein the starting mate- 11. A process for the preparation of an N-acyl-3,4-O- 2O rial is methyl N-acetyl-u-thiolincosaminide, the alkyl haisopropylidene-l-deoxylinc-osamine selected from the lide is methyl iodide, and the final products are 2-0- group consisting of compounds having the structural methyl N acetyl 3,4 O isopropylidene 1 deoxyformulae: lincosamine, 7-O-methyl-N-acetyl 3,4-O-isopropylidenefl'ls $H3 CH3 0 R O-C-H O HO-C-'H Q R O-C-H g H I I! H l g H R N-C'-H a c-uncut R -N-C-H 0 O O H cu H CH3\/ H CHa\ n C C I I R2 CH3 CH3 CH3 whereinR is selected from the group consisting of alkyl l-deoxylincosamine and 2,7-di-O-methyl-N-acetyl-3,4-0- and aralkyl containing from 1 to 11 carbon atoms, inisopropylidene-l-deoxylincosamine. elusive, and wherein R is an alkyl group having from 1 13. A process for the preparation of an O-alkyl-subto 12 carbon atoms, inclusive, which comprises: treating stituted-wthiolincosaminide selected from the group cona methyl N-acyl-a-thiolincosaminide of the formula: 40 sisting of compounds having the structural formulae:

CH3 CH3 CH3 aO-c-H HO-G-H R ni- HzN-C-H HzN-C-H HaN-C-H H0 no 0 sou H H H R2 R2 wherein R is an alkyl group having from 1 to 12 carbon atoms, inclusive, which comprises: treating a methyl N- acyl-a-thiolincosaminide of the formula:

$H HO-?-H I R -i-ll-C-H O O H wherein R is defined as above, with acetone and an acid Me catalyst to obtain a mixture of a methyl N-acyl-3,4-O- isopropylidene-a-thiolincosaminide and the oxazoline H thereof; separating the methyl N-acyl-3,4-O-isopropyliwherein R is selected from the group consisting of alkyl dene-u-thiolincosaminide from the oxazoline thereof and and aralkyl containing from 1 to 11 carbon atoms, inhydrolyzing the oxazoline to the methyl N-acyl-3,4-O- elusive, with acetone and an acid catalyst to obtain a isopropylidene-a-thiolincosaminide; alkylating this commethyl N-acyl-3,4-O-is0propylidene-a-thiolincosaminide pound with an alkyl halide selected from the group conand the oxazoline thereof; separating the methyl N-acylsisting of alkyl chlorides, alkyl bromides and alkyl iodides 3,4-O-isopropylidene-a-thiolincosaminicle from the mumin which the alkyl group has from 1 to 12 carbon atoms, line thereof and hydrolyzing the oxazo'line to the methyl inclusive, in the presence of a base; separating the thus- N-acyl-3,4-O-isopropy1idene-a-thiolincosaminide; alkylatobtained methyl N-acyl-3,4-O-isopropylidene-2-O-alkyl-aing this compound with an alkyl halide selected from the thiolincosaminide, methyl N-acyl-3,4-O-isopropylidene-7- group consisting of alkyl chlorides, alkyl bromides and O-alkyl-a-thiolincosaminide and methyl N-acyl-3,4-O-isoalkyl iodides in which the alkyl group has from 1 to 12 a-thiolincosaminide.

14. A process for the preparation of an O-alkyl-ldcoxylincosamine selected from the group consisting of compounds having the structural formulae:

wherein R is an alkyl group having from 1 to 12 carbon atoms, inclusive, which comprises: treating a methyl N- acyl-a-thiolincosaminide of the formula:

wherein R is selected from the group consisting of alkyl 40 and aralkyl containing from 1 to 11 carbon atoms, inclusive, with acetone and an acid catalyst to obtain a methyl N-acyl-3,4-O-isopropylidene-u-thiolincosaminide and the oxazoline thereof; separating said methyl N- acyl-3,4-O-isopropylidene-a-thiolincosaminide from the oxazoline thereof and hydrolyzing the oxazoline to the methyl N-acyl-3,4-O-isopropylidene-a-thiolincosaminide; alkylating this compound with an alkyl halide selected from the group consisting of alkyl chlorides, alkyl bromides and alkyl iodides in which the alkyl group has from 1 to 12 carbon atoms, inclusive, in the presence of a base; separating the thus-obtained methyl N-acyl-3,4-

O isopropylidene 1 2 O alkyl 0c thiolincosaminide, methyl N-acyl-3,4-O-isopropylidene-7-O-alkyl-a-thiolincosaminide and methyl N-acyl-3,4-O-isopropylidene-2,7- di-O-alkyl-a-thiolincosaminide from each other; desulfurizing separately each of these compounds with a nickel catalyst in a lower alkanol to obtain separately the corresponding N-acyl-Z-O-alkyb3,4-O-isopropy1idene-l--deoxylincosamine, N acyl 7 O-alkyl-3,4-O-isopropylidenel-deoxylincosamine and N-acyl-2,7-di-O-alkyl-3,4-O-is'opropylidene-l-deoxylincosarnine; separately hydrolyzing the thus-obtained compound with a mineral acid and treating the obtained products with hydrazine hydrate to obtain 2-O-a1kyl-l-deoxylincosamine, 7-O-alkyl-1-deoxylincosamine and 2,7-di-O-alkyl-l-deoxylincosamine.

References Cited Pigman: The Carbohydrates, 1957, Academic Press Inc., New York, N.Y., pp. 369-373.

LEWIS GOTTS, Primary'Examiner.

ELBERT L. ROBERTS, Examiner.

JOHNNIE R. BROWN, Assistant Examiner. 

1. AN OXAZOLINE HAVING THE STRUCTURAL FORMULA 